Psychosocial influences have been implicated in the etiology of several of the most common illnesses impacting human health (cardiovascular disease; diabetes; cancer). It has been hypothesized that these psychosocial effects are mediated through DNA-based biological changes, such as methylation alterations or telomere attrition. However, due to the paucity of research in this area, many questions remain: To what extent do epigenetic and acquired genomic changes accumulate over the human lifespan? Do childhood adversities result in biological changes that persist into adulthood? Can an adult who was exposed to childhood adversities be identified as at risk for developing disease based on their epigenetic, gene expression, telomeric, chromosomal instability, and/or cortisol level profiles? To answer these questions we will study 736 twins who have completed intense phenotypic behavioral evaluations in previous studies (completed 2 to 15 years ago) and represent two risks groups: (1) twins experiencing the extreme childhood adversity event of sexual abuse; and (2) twins experiencing a broad spectrum of social experiences. Cohort 1 (ages 40-55) will comprise a selected sample of 50 identical twin pairs who are discordant for a history of childhood sexual abuse, as well as 50 identical concordant pairs who did (25 pairs) or did not (25 pairs) experience sexual abuse as a child. The biological endpoints that will be measured and compared between co-twins for this cohort include: (1) frequencies and locations of genome-wide methylation changes using a sequence-based approach; (2) chromosome-specific telomere lengths; (3) frequencies of acquired chromosomal instability; (4) patterns of gene expression; and (4) diurnal basal salivary cortisol levels. Cohort 2 (ages 20-30) will be comprised of a normative sample of monozygotic (157 pairs) and dizygotic (111 pairs) twin pairs for whom behavioral phenotypes have been carefully determined throughout adolescence into young adulthood. The data gained from the study of these twins will provide insight as to the potential cumulative effect of multiple adversities on embedded biological changes. The biological endpoints to be measured for this cohort (for whom blood samples have been previously collected and are readily available) include: (1) frequencies and locations of genome-wide methylation changes using array based methodology; and (2) gene expression patterns. Collectively, comparisons of observed alterations in biological endpoint measures (within and between twins) to phenotypic data collected from multiple stages in the human lifespan will allow us to deduce the extent to which the observed differences in biomarkers are influenced by childhood adversity, adult adversity, and/or other environmental stressors. The data from this investigation will lead to the first direct estimate of the frequency of epigenetic, telomere length, acquired chromosomal instability, gene expression, and/or cortisol level changes that arise in adults due to childhood adversities.